Investigations using known chemical mutagens have failed to show induction of dominant lethal mutations in spermatogonial stem cells of mice. Studies with irradiation have shown that delivering a dose in two fractions increased the mutation rate, thus implying that the first fraction caused the stem cells to enter a more sensitive state by the time of the second fraction. We are investigating whether pretreatment with irradiation will sensitize spermatogonia to induction of mutations by chemical treatment following the irradiation. Comparisons are being made between groups of animals receiving the combined treatment, radiation alone or only chemical treatment for induction of dominant lethals and chromosome aberrations.